Pulsatile Delivery of Fexofenadine Hydrochloride Pulsincap by Box-Behnken Design

Objective: Fexofenadine hydrochloride is a selective peripheral H1-blocker, used for allergy symptoms, such as hay fever and urticaria. Allergic symptoms are aggressive during early morning hours, so a pulsatile delivery system with a lag time of 4-5 hours was formulated and optimized by Box-Behnken design. Materials and Methods: Pulsincap system using formaldehyde-treated capsules and hydrogel plug. Box-Behnken design was applied for optimization in which three independent variables, X1= Drug: polymer ratio, X2 = Polymer: polymer ratio (Ethylcellulose: HPMC E15) and X3 = Plug weight were selected. Three dependent variables R1 = Percent release of drug after 4 hours, R2 = percent release after 10 hours and R3 = Lag time were selected. Results: FTIR and DSC studies confirmed compatibility of drug and excipients. The empty formaldehyde-treated capsules were evaluated for physical appearance, solubility, capsule dimensions and formaldehyde content. Hydrogel plugs, powder blend and pulsincap formulations were evaluated for Physico-chemical parameters and all the parameters were within acceptable limits. Contour plots and Response surface plots indicated that as Drug: Polymer ratio (X1) and Plug weight (X3) increased, Lag time increased but% drug release decreased. As Polymer: Polymer ratio (X2) increased, the lag time was at a moderate level. Predicted vs actual responses showed the correlation of 0.786 for% release in 4hrs, 0.9744 for% release in 10hrs and 0.6281 for lag time. Optimized formulation G1 was suggested by design (with criteria 4.5-6hrs lag time, 10-20% release in 4hrs & 60-70% drug release within 10hrs). The optimised formulation was stable. Conclusion: Pulsincap system of Fexofenadine hydrochloride can be obtained by using retarding polymers like ethyl cellulose, HPMC E15 and formaldehyde cross-linked capsules.

A Concise Insight on Pulsatile Drug Delivery System: An Outlook towards its Development

In pharmaceutical science, the pulsatile drug delivery system gains more attraction because of their number of benefits over the other dosage forms. In these systems, the drug is released at right time at the right site of action, and in the right amount, it is the most beneficial and important characteristic of the PDDS system due to that the patient compliance is increased, and the drug release is after a well-defined lag time. Moreover, this system is designed according to the circadian rhythm of the body. Because the disease has a predictable cyclic rhythm, such as Arthritis, diabetes mellitus, asthma, peptic ulcer, hypertension, cardiovascular disease the PDDS is more effective than other dosage forms.This system is a more time-specific and site-specific drug delivery system. In this system the drug is released as a pulse. The mechanism of PDDS is first diffusion then erosion and then osmosis. For the drug having a high first-pass effect and having a high risk of toxicity and side effects, these systems can be very useful. And to reduce dosing frequency and improve patient compliance this system is very helpful. There are various methods present like, single-unit systems and multiple-unit systems – which included capsular system, pulsatile delivery by osmosis, pulsatile delivery by erosion of membrane, delivery by rupture of membrane, etc.